TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16512	49759;49760;49761	chr2:178613275;178613274;178613273	chr2:179478002;179478001;179478000
N2AB	14871	44836;44837;44838	chr2:178613275;178613274;178613273	chr2:179478002;179478001;179478000
N2A	13944	42055;42056;42057	chr2:178613275;178613274;178613273	chr2:179478002;179478001;179478000
N2B	7447	22564;22565;22566	chr2:178613275;178613274;178613273	chr2:179478002;179478001;179478000
Novex-1	7572	22939;22940;22941	chr2:178613275;178613274;178613273	chr2:179478002;179478001;179478000
Novex-2	7639	23140;23141;23142	chr2:178613275;178613274;178613273	chr2:179478002;179478001;179478000
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-7
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.107
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
V/L	rs2056682853	None	0.997	N	0.647	0.325	0.610013871061	gnomAD-4.0.0	1.20194E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31426E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
V/A	0.8947	likely_pathogenic	0.7279	pathogenic	-2.009	Highly Destabilizing	0.999	D	0.633	neutral	D	0.560612016	None	None	N
V/C	0.9637	likely_pathogenic	0.8917	pathogenic	-1.492	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
V/D	0.998	likely_pathogenic	0.996	pathogenic	-2.678	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/E	0.9892	likely_pathogenic	0.9813	pathogenic	-2.403	Highly Destabilizing	1.0	D	0.833	deleterious	D	0.757654599	None	None	N
V/F	0.9182	likely_pathogenic	0.8723	pathogenic	-1.187	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/G	0.9545	likely_pathogenic	0.9061	pathogenic	-2.581	Highly Destabilizing	1.0	D	0.846	deleterious	D	0.757654599	None	None	N
V/H	0.9978	likely_pathogenic	0.9954	pathogenic	-2.327	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/I	0.1611	likely_benign	0.1228	benign	-0.383	Destabilizing	0.998	D	0.539	neutral	None	None	None	None	N
V/K	0.9942	likely_pathogenic	0.9924	pathogenic	-1.713	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
V/L	0.8184	likely_pathogenic	0.69	pathogenic	-0.383	Destabilizing	0.997	D	0.647	neutral	N	0.47751996	None	None	N
V/M	0.8329	likely_pathogenic	0.6848	pathogenic	-0.46	Destabilizing	1.0	D	0.736	prob.delet.	D	0.661344004	None	None	N
V/N	0.9927	likely_pathogenic	0.9811	pathogenic	-2.187	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/P	0.9946	likely_pathogenic	0.9898	pathogenic	-0.901	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
V/Q	0.9877	likely_pathogenic	0.9771	pathogenic	-1.929	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
V/R	0.9915	likely_pathogenic	0.9895	pathogenic	-1.733	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/S	0.9743	likely_pathogenic	0.9113	pathogenic	-2.793	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
V/T	0.9376	likely_pathogenic	0.829	pathogenic	-2.352	Highly Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
V/W	0.9986	likely_pathogenic	0.9975	pathogenic	-1.685	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/Y	0.9932	likely_pathogenic	0.987	pathogenic	-1.273	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.